BEST PRACTICE MANAGEMENT: CARDIOVASCULAR RISKS

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1 BEST PRACTICE MANAGEMENT: CARDIOVASCULAR RISKS Neil R Poulter ICCH, Imperial College London BHIVA: October 10th, 2008

2 Background CVD is the biggest single killer in the world CVD rates are increasing High prevalence of CV risk in society mirrored and amplified in HIV population Increasing age at presentation Long-term survival on therapy Independent effects of HIV on lipids, vascular function.

3 HIV/AIDS in the United States: Disease trends in deaths with HIV Percentage * * * * * * * * * * * * * * Liver disease (other than viral hepatitis) Kidney disease Heart disease (other than cardiac arrest) Wasting /cachexia 3 2 Dementia/encephalopathy 1 0 Acute pancreatitis Year Decrease in the proportion of deaths directly attributable to HIV or an AIDS-defining conditions Increase in the proportion of deaths associated with liver, kidney and heart disease Selik et al. JAIDS 2002;29:

4 CV risk factors in an HIV-infected population: the DAD study 0 Prevalence (%) Smoking TGs 203 mg/dl (2.3 mmol/l) HDL-C 35 mg/dl (0.9 mmol/l) Lipodystrophy Age (>45 yr male; >55 yr female) TC 239 mg/dl (6.2 mmol/l) Family history of CHD Hypertension BMI >30 kg/m 2 Diabetes Previous CHD 11% 8.5% 3.5% 2.5% 1% 26% 25% 25% 22% 34% Un-modifiable 52% Potentially modifiable Lipid & adipose tissue abnormalities potentially modifiable CHD: coronary heart disease; BMI: body mass index; DAD: Data Collection of Adverse Events Friis-Moller N et al. AIDS 2003;17:

5 Global Burden of Disease: Change in rank order of disability (DALY s) for the 10 leading causes, 1990 & Disease or injury 1. Acute lower respiratory infections 2. HIV / AIDS 3. Perinatal conditions 4. Diarrhoeal diseases 5. Unipolar major depression 6. Ischaemic heart disease 7. Cerebrovascular disease 8. Malaria 9. Road traffic accidents 10. Chronic obstructive pulmonary disorder 2020 Disease or injury 1. Ischaemic heart disease 2. Unipolar major depression 3. Road traffic accidents 4. Cerebrovascular disease 5. Chronic obstructive pulmonary disorder 6. Lower respiratory infections 7. Tuberculosis 8. War 9. Diarrhoeal diseases 10. HIV

6 Do we know the real causes of CVD?

7 Changes in death rates from CHD, men and women aged 35 74, between 1989 & 1999, selected countries Australia Norway Luxembourg Finland Netherlands UK Sweden Czech Republic Ireland Italy France Austria Portugal USA Lithuania Estonia Greece Spain Azerbaijan Japan Romania Kazakstan Croatia Belarus Ukraine Men Women % decrease % increase

8 INTERHEART study 9 risk factors* account for 90% of PAR** in men and 94% in women Men, women, young, old, 4 continents. * Smoking, ApoB/ApoA, hypertension, diabetes mellitus, abdominal obesity, psychosocial factors, fresh fruit & vegetables, alcohol, physical activity ** Population attributable risk

9 Absolute Risk of CVD Over 5 Years in Patients by Systolic Blood Pressure at Specified Levels of Other Risk Factors* 50 5-Year CVD Risk per 100 People (%) % 33% 24% 18% 12% 6% 3% <1% Reference +TC = 7 mmol/l +Smoker +HDL = 1 mmol/l +Male +Diabetes +60 years CVD = cardiovascular disease; TC = total cholesterol. *Risks are given for systolic BP levels from left to right: 110, 120, 130, 140, 150, 160, 170, 180 mm Hg Jackson R et al. Lancet. 2005;365:

10 Strategies which do not incorporate such a [risk assessment] approach are likely to be less cost-effective... But BHS IV: 2004

11 ESH-ESC Guidelines 2007

12 High CVD Risk Regions, Risk Based on Total Cholesterol Women Non-smoker Smoker Age Non-smoker Smoker Men Cholesterol (mmol) mg/dl 15% and over 10% 14% 6 9% 4 5% 3% 2% 1% < 1% 10-year risk of fatal CVD in areas of high CVD risk

13 Non-diabetic men: Risk Assessment SBP SBP SBP Non-smoker Smoker Age under 50 years TC: HDL TC: HDL TC: HDL Copyright University of Manchester SBP Age under years SBP Age 60 and over SBP TC: HDL TC: HDL TC: HDL CVD risk over next 10 years <10% 10 20% >20% 10% 20% CVD risk over next 10 years 30% SBP = systolic blood pressure mmhg TC: HDL = serum total cholesterol to HDL cholesterol ratio

14 Non-diabetic Women: Risk Assessment

15 Global mortality 2000: Impact of hypertension and other health risk factors High BP Tobacco High cholesterol Underweight Unsafe sex High BMI Physical inactivity Alcohol Developing region Developed region Attributable mortality, in millions (total: 55,861,000) Adapted from Ezzati M et al. Lancet 2002;360:

16 BP treatment threshold JNC 7 ESH-ESC WHO-ISH NICE/BHS /90 140/90 All risk strata 140/90 160/100 - Inc? low risk 130/85 v high and high risk Consider resources 140/90 10 year CV risk 20%

17 Choosing drugs for patients newly diagnosed with hypertension: NICE/BHS NICE/BHS algorithm: June 2006

18 Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs Class of drug Compelling indications Possible indications Caution Compelling contraindications Alphablockers ACEinhibitors ARBs Benign prostatic hypertrophy Heart failure, LV dysfunction, post MI or established CVD, Type I diabetic nephropathy, 2 o stroke prevention ACE inhibitorintolerance, Type II diabetic nephropathy, hypertension with LVH, heart failure in ACEintolerant patients, post MI Chronic renal disease, Type II diabetic nephropathy, proteinuric renal disease LV dysfunction post MI, intolerance of other antihypertensive drugs, proteinuric renal disease, chronic renal disease, heart failure Postural hypotension, heart failure Renal impairment PVD Renal impairment PVD Urinary incontinence Pregnancy, renovascular disease Pregnancy, renovascular disease

19 BP targets JNC 7 ESH-ESC WHO-ISH NICE/BHS 2006 <140/90 <140/90 SBP <140 <140/85 DM renal <130/80 lower if tolerated DM <130/80 DM renal CVD <130/80 DM renal CVD <130/80 N.B. systolic goal JNC VII 2003, ESH-ESC 2003, WHO-ISH 2003, BHS IV 2004

20 Addressing: LIPIDS

21 Lipid thresholds for treatment Based on CVD Risk estimation All patients with established CVD or diabetes (greater than age 40) should be considered for statin treatment All adults >40 years without established CVD or diabetes should be considered for statin treatment if they have: A risk of 20% of developing CVD over the next 10 years All adults with a TC:HDL ratio >6 should be considered for statin use, irrespective of risk status For apparently healthy individuals with a 10 year total CVD risk <20%, appropriate lifestyle advice should still be given Heart 2005;91(suppl V):v1-52

22 Targets* and considerations for high-risk patients ESC JBS2 Total cholesterol mmol/l* LDL Cholesterol mmol/l* HDL cholesterol mmol/l Triglyceride mmol/l <4.5 <1.8 >1.0 - men >1.2 -women <1.7 <4.0 <2.0 >1.0 - men >1.2 -women <1.7 Heart 2005;91(suppl V):v1-and Joint ESC/EASD guidelines on diabetes, pre-diabetes, and cardiovascular diseases 52

23 TREATMENT OF DYSLIPIDAEMIA Treatment pathways Isolated Hypercholesterolaemia Total cholesterol (>5) + LDL cholesterol (>3) Combined Hyperlipidaemia Total cholesterol (>5) + Triglycerides (>5.4) Priority is to treat LDL cholesterol to target of <3 mmol/l Isolated hypertriglyceridaemia Fasting Triglycerides > 5.4 Priority is to reduce risk of pancreatitis by lowering tg <4.5 Prescribe Statin TG> 5.4mmol/L <10mmol- TG >10mmol/L Up titrate statin as required. If unable to get to TC and LDL targets refer. If unable to get TG to target refer. *Combination therapy of statin and Fibric acid derivative has increased potential for muscle pain/myositis Monitor CK 8-10 wks after starting combination therapy **For Low HDL cholesterol with significant vascular risk Niaspan may be considered as alternative to fibric acid derivative

24 TREATMENT OF DYSLIPIDAEMIA Treatment pathways Isolated Hypercholesterolaemia Statins: Drugs of Choice Combined Hyperlipidaemia If patient tolerates above dose of statin but is still Prescribe Statin TG> not to target - refer. 5.4mmol/L Patients not tolerating higher doses of statin - refer. <10mmol- In high risk patients Rosuvastatin 5mg, 10mg or 20 mg may be used. If 40mg needed - refer Up titrate statin as required. If unable to get to TC and LDL targets refer. Isolated hypertriglyceridaemia Total cholesterol (>5) + Total cholesterol (>5) + Triglycerides (>5.4) Fasting Triglycerides > 5.4 LDL cholesterol (>3) Priority is to treat LDL cholesterol to Priority is to reduce risk of TC < 6mmol/L pravastatin target 20-40mg of <3 mmol/l use as first line treatment pancreatitis by lowering tg TC >6mmol/L atorvastatin 10-20mg use as first line treatment. <4.5 Avoid using any dose of simvastatin or atorvastatin higher than 20mg dose TG >10mmol/L If unable to get TG to target refer. *Combination therapy of statin and Fibric acid derivative has increased potential for muscle pain/myositis Monitor CK 8-10 wks after starting combination therapy **For Low HDL cholesterol with significant vascular risk Niaspan may be considered as alternative to fibric acid derivative

25 Addressing: GLUCOSE

26 The metabolic syndrome: Many different proposed definitions 1,2,3,4 Currently recommended IDF definition: Waist >94cm (men), >80 cm (women) plus any 2 of FPG > 5.6mmol/L HDL < 1.0mmol/L (men), <1.3 mmol/l (women) TGs >1.7 mmol/l SBP/DBP >130/85 mmhg 1,2,3,4 refs to be sourced Dekker JM. Circulation 2005;112:66

27 Modified NICE DM guideline 2008* HbA 1 C > 6.5% after trial of lifestyle measures metformin A sulfonylurea may be considered for non overweight or if glucose levels are particularly high HbA1C>6.5% HbA 1 C<6.5% Metformin and sulfonylurea Monitor for expected REFER *REF NICE website

28 When to refer Glycated HbA1c >7.5 on 2 anti diabetic medications. Remember all diabetics need retinal screening and peripheral neuropathy screening- consider referral to diabetic clinic

29 Global risk estimation: problems and issues Wrong name Accuracy vs simplicity CHD vs CVD Morbidity vs mortality Short-term absolute risk ageist and sexist Change in culture: prevention vs cure Evidence-based?

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